DESCRIPTION: (Verbatim) Tissue engineering offers considerable promise for temporomandibular (TMJ) joint reconstruction, a pressing clinical problem. To create durable engineered joint implants, the effects of scaffold material and architecture on tissue regeneration and function must be understood. To fill this vital need, we must be able to systematically study controlled scaffold architecture effects on bone regeneration, bone-cartilage regeneration, and load bearing capability. In this BRP, we will determine the effects of designed and fabricated internal architectures on bone regeneration by bone marrow stromal cells in an in vivo model of osteogenesis. We will mechanically test these architectures to determine load carrying capability. To test bone-cartilage interface regeneration in vivo, we will create a scaffold interface design seeded with bone marrow stromal cells on one half of the scaffold (bone side) and auricular chondrocytes on the other half (cartilage side), creating a bone-cartilage interface inside the scaffold. Finally, we will then engineer a prototype Conylar Ramus Unit (CRU) based on the most promising data from the bone-bone and bone-cartilage scaffold studies. The primary goals of this BRP are to: 1) Determine how two scaffold materials (hydroxyapatite (HA) and polyanhydride and four porosity variations within controlled architectures affect bone regeneration and load carrying capability. 2) Determine how scaffold interface designs using HA and polyanhydride for the bone half and polyanhydride and PGA for the cartilage half affect bone-cartilage interface regeneration 3) Test one prototype CRU scaffold that incorporates the best results from 1 and 2 in an in vivo minipig model at 3, 6 and 12 months. The prototype CRU will have designed external shape and scaffold architecture. Our first two specific aims are to apply image-based optimal design and solid free-form fabrication to create the scaffolds. The remaining four specific aims are to investigate the performance of these scaffolds mechanically and using subcutaneous models, resulting in the in vivo minipig test of a prototype CRU.